The purpose of this research is to specify how hormones present during perinatal developmental periods influence male and female reproductive competence throughout their life span. The amount of androgen or a hormone to which it is converted in reproductive organs and the brain, not only determines development of male and female organs and behavior potentiality but also the time course of important physiological events. The age at which estrous cycles become irregular or cease will be controlled by administering steroid hormones during fetal and neonatal stages. Modification in the functional interrelationships between the hypothalamus, pituitary and ovaries which mediate experimentally induced premature disruption of fertility will be related to naturally occurring senile states of persistent estrus, repetitive pseudopregnancy and persistent anestrus. Attention will be focused in these studies on modifications in the luteinizing hormone-releasing hormone (LH-RH) system which integrates neural and hormonal events related to reproduction. LH-RH neurons and content, analyzed by immunocytochemical and radioimmunoassay methods, will be related to the perinatal hormone treatments and consequent senile conditions. Age-related declines in female receptivity and male sexual responses will be quantitatively described throughout the lifespan of normal and experimentally manipulated animals. Hormonal, in particular ovarian secretions, and experiential circumstances which retard or accelerate rate of decline in these behaviors are being examined. The extent to which the decrements in female behavior are related to diminished responsiveness to estrogen and progesterone and male behavior to reduced sensitivity to testosterone will be determined. The cellular basis of the observed losses in hormone utilization will be correlated with modifications in receptor protein synthesis. The hypothesis that estrogen in low dosages facilitates androgen action and in high dosages produces untoward alteration in cells which impairs responsiveness to hormones mediating both male and female behavior will be tested. The research will also localize regions in the brain modified by hormones.